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Masanori Yasuo,* Yoshiaki Kitaguchi,* Yayoi Tokoro, Makoto Kosaka, Yosuke Wada, Takumi Kinjo, Atsuhito Ushiki, Hiroshi Yamamoto, Masayuki Hanaoka The First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan*These authors contributed equally to this workCorrespondence: Masanori YasuoThe First Department of Internal Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, JapanTel +81 263 37 2631Fax +81 263 36 3722Email yasumasa@shinshu-u.ac.jpBackground: Obstructive ventilatory disturbances occur in both chronic obstructive pulmonary disease (COPD), a typical disease representative of peripheral airway obstruction, and central airway obstruction (CAO). Pulmonary function tests (PFTs), which depend on patient effort, are traditionally used to evaluate lung function. The forced oscillation technique (FOT) is an effort-independent method for examining lung function during tidal breathing. The FOT is used universally to assess respiratory function in patients with COPD. Several studies have measured FOT to assess ventilatory disturbances in CAO. The results showed that FOT measurements in patients with CAO were similar to those reported in patients with COPD. However, no studies have compared FOT measurements directly between CAO and COPD. The aim of this study was to identify differences in ventilatory disturbances between peripheral and central airway obstructions in COPD and CAO, before patients received pharmacological therapy or bronchoscopic interventions, respectively.Patients and Methods: We retrospectively included 16 patients with CAO (10 cases of tracheal obstruction and 6 cases of bronchial obstruction) and 75 treatment-naïve patients with COPD (60 cases in Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage II and 15 cases in GOLD stage III) that were admitted from December 2013 to May 2017. Prior to treatment, patients were examined with the FOT and PFTs.Results: All parameters measured with the FOT in the inspiratory phase were significantly worse in patients with CAO than in patients with COPD. The PFTs showed that the CAO group had a significantly lower peak expiratory flow rate. In the airway wall thickening phenotype of COPD, a difference between the inspiratory and expiratory phases of the resonance frequency (ΔFres) was the best indicator for distinguishing between peripheral and central airway obstructions.Conclusion: This study compared differences between CAO and COPD (mainly GOLD stage II). We found that the FOT measurement, ΔFres, was the optimal indicator of the difference between the airway wall thickening COPD phenotype and CAO. Thus, the difference might be due to mechanical changes that occur in COPD with airway wall thickening.Keywords: forced oscillation technique, pulmonary function test, quality of life, central airway obstruction, COPD

Abstract Background Bronchial Thermoplasty (BT) is an endoscopic treatment for severe asthma using radiofrequency energy to target airway remodeling including smooth muscle. The correlation of pulmonary function tests and BT response are largely unknown. Forced Oscillation Technique (FOT) is an effort-independent technique to assess respiratory resistance (Rrs) by using pressure oscillations including small airways. Aim To investigate the effect of BT on pulmonary function, assessed by spirometry, bodyplethysmography and FOT and explore associations between pulmonary function parameters and BT treatment response. Methods Severe asthma patients recruited to the TASMA trial were analyzed in this observational cohort study. Spirometry, bodyplethysmography and FOT measurements were performed before and 6 months after BT. Asthma questionnaires (AQLQ/ACQ-6) were used to assess treatment response. Results Twenty-four patients were analyzed. AQLQ and ACQ improved significantly 6 months after BT (AQLQ 4.15 (±0.96) to 4.90 (±1.14) and ACQ 2.64 (±0.60) to 2.11 (±1.04), p = 0.004 and p = 0.02 respectively). Pulmonary function parameters remained stable. Improvement in FEV1 correlated with AQLQ change (r = 0.45 p = 0.03). Lower respiratory resistance (Rrs) at baseline (both 5 Hz and 19 Hz) significantly correlated to AQLQ improvement (r = − 0.52 and r = − 0.53 respectively, p = 0.01 (both)). Borderline significant correlations with ACQ improvement were found (r = 0.30 p = 0.16 for 5 Hz and r = 0.41 p = 0.05 for 19 Hz). Conclusion Pulmonary function remained stable after BT. Improvement in FEV1 correlated with asthma questionnaires improvement including AQLQ. Lower FOT-measured respiratory resistance at baseline was associated with favorable BT response, which might reflect targeting of larger airways with BT. Trial registration ClinicalTrials.gov Identifier: NCT02225392; Registered 26 August 2014.

Background: Forced oscillation technique (FOT) is a technique to measure the mechanical properties of the lung. The present study was aimed to develop regression equations of within- and whole-breath respiratory impedance (Zrs) of healthy Indian adults. Methods: Total 323 adults were sequentially screened. Smokers, individuals with respiratory symptoms or diseases, and unable to perform acceptable FOT were excluded. Within- and whole-breath resistance (Rrs) and reactance (Xrs) were measured at 5, 11, and 19 Hz by Resmon Pro® Full device. The regression equations of within- and whole-breath Rrs and Xrs were generated separately for men and women by multiple linear regression models. Results: The FOT data of 253 individuals (122 men) aged 18–81 years were included in the analysis. The magnitudes of whole-breath Rrs at 5 Hz (4.53 ± 1.05 cmH2O/L/s in women vs. 3.26 ± 1.05 cmH2O/L/s in men; P = 0.000) and whole-breath Xrs at 5 Hz (−1.23 ± 0.66 cmH2O/L/s in women vs. −1.00 ± 0.54 cmH2O/L/s in men; P = 0.003) of women were significantly of higher magnitude as compared to men. The standing height was the best determinant of Zrs, followed by body weight; the effect of age was negligible and was observed in men only. The magnitudes of both Rrs and Xrs decrease with an increase in standing height of both men and women. Conclusions: The present study provides regression equations of within- and whole-breath respiratory impedance of Indian adults.

Sabine C Zimmermann, 1–3 Cindy Thamrin, 1 Andrew SL Chan, 2, 3 Amy Bertolin, 1 David G Chapman, 1, 4 Gregory G King 1–3 1The Woolcock Emphysema Centre, Woolcock Institute of Medical Research, The University of Sydney, Glebe, NSW 2037, Australia; 2The Northern Clinical School, Faculty of Medicine and Health Sciences, The University of Sydney, Camperdown, NSW 2006, Australia; 3Department of Respiratory Medicine, Royal North Shore Hospital, St Leonards, NSW 2065, Australia; 4School of Life Sciences, Faculty of Science, University of Technology Sydney, Ultimo, NSW 2007, AustraliaCorrespondence: Sabine C ZimmermannThe Woolcock Institute of Medical Research, 431 Glebe Point Road, Glebe, NSW 2037, AustraliaTel +61 2 9114 0404Fax +61 2 9114 0010Email sabine.zimmermann@sydney.edu.auRationale: Pulmonary rehabilitation for chronic obstructive pulmonary disease (COPD) reduces dyspnoea and improves exercise capacity and quality of life. The improvement in exercise capacity is variable and unpredictable, however. Respiratory system impedance obtained by forced oscillation technique (FOT) as a measure of ventilatory impairment in COPD may relate to improvement in exercise capacity with pulmonary rehabilitation. We aimed to determine if baseline FOT parameters relate to changes in exercise capacity following pulmonary rehabilitation.Methods: At the start of rehabilitation, 15 COPD subjects (mean(SD) 75.2(6.1) years, FEV1 z-score − 2.61(0.84)) had measurements by FOT, spirometry, plethysmographic lung volumes and 6-minute walk distance (6MWD). Respiratory system resistance (Rrs) and reactance (Xrs) parameters as the mean over all breaths (Rmean, Xmean), during inspiration only (Rinsp, Xinsp), and expiratory flow limitation (DeltaXrs = Xinsp−Xexp), were calculated. FOT and 6MWD measurements were repeated at completion of rehabilitation and 3 months after completion.Results: At baseline, Xrs measures were unrelated to 6MWD. Xinsp improved significantly with rehabilitation (from mean(SD) − 2.35(1.02) to − 2.04(0.85) cmH 2O.s.L− 1, p=0.008), while other FOT parameters did not. No FOT parameters related to the change in 6MWD at program completion. Baseline Xmean, DeltaXrs, and FVC z-score correlated with the change in 6MWD between completion and 3 months after completion of rehabilitation (rs=0.62, p=0.03; rs=− 0.65, p=0.02; and rs=0.62, p=0.03, respectively); with worse ventilatory impairment predicting loss of 6MWD. There were no relationships between Rrs parameters, FEV1 or FEV1/FVC z-scores and changes in 6MWD.Conclusion: Baseline reactance parameters may be helpful in predicting those patients with COPD at most risk of loss of exercise capacity following completion of pulmonary rehabilitation.Keywords: COPD, forced oscillation technique, reactance, pulmonary rehabilitation, six-minute walk test, quality of life

Background: The diagnosis of mild-moderate equine asthma (MEA) can be confirmed by airway endoscopy, bronchoalveolar lavage fluid (BALf) cytology, and lung function evaluation by indirect pleural pressure measurement. Oscillometry is a promising pulmonary function test method, but its ability to detect subclinical airway obstruction has been questioned., Objectives: To evaluate the differences in lung function measured by oscillometry between healthy and MEA-affected horses., Study Design: Prospective case-control clinical study., Methods: Thirty-seven horses were divided into healthy and MEA groups, based on history and clinical score; the diagnosis of MEA was confirmed by airway endoscopy and BALf cytology. Horses underwent oscillometry at frequencies ranging from 2 to 6 Hz. Obtained parameters included whole-breath, inspiratory, expiratory, and the difference between inspiratory and expiratory resistance (Rrs) and reactance (Xrs). Differences between oscillometry parameters at different frequencies were evaluated within and between groups by repeated-measures two-way ANOVA and post hoc tests with Bonferroni correction. Frequency dependence was compared between groups by t test. For significant parameters, a receiver operating characteristics curve was designed, cut-off values were identified and their sensitivity and specificity were calculated. Statistical significance was set at p < 0.05., Results: No significant differences in Xrs and Rrs were observed between groups. The frequency dependence of whole-breath and inspiratory Xrs significantly differed between healthy (respectively, -0.03 ± 0.02 and -0.05 ± 0.02 cmH 2 O/L/s) and MEA (-0.1 ± 0.03 and -0.2 ± 0.02 cmH 2 O/L/s) groups (p < 0.05 and p < 0.01). For inspiratory Xrs frequency dependence, a cut-off value of -0.06 cmH 2 O/L/s was identified, with 86.4% (95% CI: 66.7%-95.3%) sensitivity and 66.7% (95% CI: 41.7%-84.8%) specificity., Main Limitations: Sample size, no BALf cytology in some healthy horses., Conclusions: Oscillometry can represent a useful non-invasive tool for the diagnosis of MEA. Specifically, the evaluation of the frequency dependence of Xrs may be of special interest., (© 2024 The Author(s). Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.)

Background: Tidal expiratory flow limitation (EFLT) is common among COPD patients. Whether EFLT changes during sleep and can be abolished during home ventilation is not known.Methods: COPD patients considered for noninvasive ventilation used a ventilator which measured within-breath reactance change at 5 Hz (∆Xrs) and adjusted EPAP settings to abolish EFLT. Participants flow limited (∆Xrs > 2.8) when supine underwent polysomnography (PSG) and were offered home ventilation for 2 weeks. The EPAP pressure that abolished EFLT was measured and compared to that during supine wakefulness. Ventilator adherence and subjective patient perceptions were obtained after home use.Results: Of 26 patients with supine EFLT, 15 completed overnight PSG and 10 the home study. In single night and 2-week home studies, EFLT within and between participants was highly variable. This was unrelated to sleep stage or body position with only 14.6% of sleep time spent within 1 cmH2O of the awake screening pressure. Over 2 weeks, mean EPAP was almost half the mean maximum EPAP (11.7 vs 6.4 cmH2O respectively). Group mean ∆Xrs was ≤ 2.8 for 77.3% of their home use with a mean time to abolish new EFLT of 5.91 min. Adherence to the ventilator varied between 71 and 100% in prior NIV users and 36-100% for naïve users with most users rating therapy as comfortable.Conclusions: Tidal expiratory flow limitation varies significant during sleep in COPD patients. This can be controlled by auto-titrating the amount of EPAP delivered. This approach appears to be practical and well tolerated by patients.Trial Registration: The trial was retrospectively registered at CT.gov NCT04725500. [ABSTRACT FROM AUTHOR]

High-frequency oscillatory ventilation (HFOV) is a type of mechanical ventilation with a protective potential characterized by a small tidal volume. Unfortunately, HFOV has limited monitoring of ventilation parameters and mechanical parameters of the respiratory system, which makes it difficult to adjust the continuous distension pressure (CDP) according to the individual patient's airway status. Airway resistance Raw is one of the important parameters describing the mechanics of the respiratory system. The aim of the presented study was to verify in vitro whether the resistance of the respiratory system Rrs can be reliably determined during HFOV to evaluate Raw in pediatric and adult patients. An experiment was performed with a 3100B high-frequency oscillator, a physical model of the respiratory system, and a pressure and flow measurement system. The physical model with different combinations of resistance and compliance was ventilated during the experiment. The resistance Rrs was calculated from the impedance of the physical model, which was determined from the spectral density of the pressure at airway opening and the spectral cross-density of the gas flow and pressure at airway opening. Rrs of the model increased with an added resistor and did not change significantly with a change in compliance. The method is feasible for monitoring respiratory system resistance during HFOV and has the potential to optimize CDP settings during HFOV in clinical practice. [ABSTRACT FROM AUTHOR]

The current gold standard to assess respiratory mechanics in mice is oscillometry, a technique from which several readouts of the respiratory system can be deduced, such as resistance and elastance. However, these readouts are often not altered in mouse models of asthma. This is in stark contrast with humans, where asthma is generally associated with alterations when assessed by either oscillometry or other techniques. In the present study, we have used double-chamber plethysmography (DCP) to evaluate the breathing pattern and the degree of airflow obstruction in a mouse model of asthma. Female C57BL/6 and BALB/c mice were studied at day 1 using DCP, as well as at day 11 using both DCP and oscillometry following a once-daily exposure to either house-dust mite (HDM) or saline for 10 consecutive days. All DCP readouts used to describe either the breathing pattern (e.g., tidal volume and breathing frequency) or the degree of airflow obstruction (e.g., specific airway resistance) were different between mouse strains at day 1. Most of these strain differences persisted at day 11. Most oscillometric readouts (e.g., respiratory system resistance and elastance) were also different between strains. Changes caused by HDM were obvious with DCP, including decreases in tidal volume, minute ventilation, inspiratory time and mid-tidal expiratory flow and an increase in specific airway resistance. HDM also caused some strain specific alterations in breathing pattern, including increases in expiratory time and end inspiratory pause, which were only observed in C57BL/6 mice. Oscillometry also detected a small but significant increase in tissue elastance in HDM versus saline-exposed mice. DCP successfully identified differences between C57BL/6 and BALB/c mice, as well as alterations in mice from both strains exposed to HDM. We conclude that, depending on the study purpose, DCP may sometimes outweigh oscillometry. [ABSTRACT FROM AUTHOR]

Background: Thoracic surgery is a recommended treatment option for non-small cell lung cancer patients. An important part of a patient’s therapy, which helps to prevent postoperative complications and improve quality of life, is pulmonary rehabilitation (PR). The aim of this study was to assess whether the implementation of physical activity has an influence on forced oscillation technique (FOT) values in patients after thoracic surgery due to lung cancer. Methods: In this observational study, we enrolled 54 patients after thoracic surgery due to lung cancer, 49 patients with idiopathic interstitial fibrosis (IPF), and 54 patients with chronic obstructive pulmonary disease/asthma–COPD overlap (COPD/ACO). All patients were subjected to three weeks of in-hospital PR and assessed at the baseline as well as after completing PR by FOT, spirometry, grip strength measurement, and the 6-min walk test (6MWT). Results: We observed differences between FOT values under the influence of physical activity in studied groups, mostly between patients after thoracic surgery and COPD/ACO patients; however, no significant improvement after completing PR among FOT parameters was noticed in any group of patients. Improvements in the 6MWT distance, left hand strength, and right hand strength after PR were noticed (p < 0.001, 0.002, and 0.012, respectively). Conclusions: Three weeks of pulmonary rehabilitation had no impact on FOT values in patients after thoracic surgery due to lung cancer. Instead, we observed improvements in the 6MWT distance and the strength of both hands. Similarly, no FOT changes were observed in IPF and COPD/ACO patients after completing PR.

Background and objective: In 2014, a 6‐week‐long fire at the Hazelwood coal mine exposed residents in the adjacent town of Morwell to high concentrations of fine particulate matter with an aerodynamic diameter < 2.5 μm (PM2.5). The long‐term health consequences are being evaluated as part of the Hazelwood Health Study. Methods: Approximately 3.5–4 years after the mine fire, adults from Morwell (n = 346) and the comparison town Sale (n = 173) participated in the longitudinal Respiratory Stream of the Study. Individual PM2.5 exposure was retrospectively modelled. Lung mechanics were assessed using the forced oscillation technique (FOT), utilizing pressure waves to measure respiratory system resistance (Rrs) and reactance (Xrs). Multivariate linear regression was used to evaluate associations between PM2.5 and transformed Rrs at 5 Hz, area under the reactance curve (AX5) and Xrs at 5 Hz controlling for key confounders. Results: There were clear dose–response relationships between increasing mine fire PM2.5 and worsening lung mechanics, including a reduction in post‐bronchodilator (BD) Xrs5 and an increase in AX5. A 10 μg/m3 increase in mine fire‐related PM2.5 was associated with a 0.015 (95% CI: 0.004, 0.027) reduction in exponential (Xrs5) post‐BD, which was comparable to 4.7 years of ageing. Similarly, the effect of exposure was associated with a 0.072 (0.005, 0.138) increase in natural log (lnAX5) post‐BD, equivalent to 3.9 years of ageing. Conclusion: This is the first study using FOT in adults evaluating long‐term respiratory outcomes after medium‐term ambient PM2.5 exposure to coal mine fire smoke. These results should inform public health policies and planning for future events. [ABSTRACT FROM AUTHOR]

Abstract Lung function impairment is common in Congenital Diaphragmatic Hernia (CDH) survivors. The aim of this study was to evaluate, in children who underwent CDH surgical repair, mid and long-term consequences on respiratory impedance, investigating the impact of CDH on both resistance and reactance parameters, as well as bronchodilator response. Forced Oscillation Technique (FOT) parameters were collected from 12 patients (2–11 years). Resistance and reactance values at 8 Hz (Rrs8, Xrs8) and the area under the reactance curve (AX) were measured pre and post-salbutamol. Quantitative variables were compared using Mann-Whitney U test. Differences of categorical variables were evaluated using Fisher exact test. Statistically significant differences between measured and predicted values for Rrs8 (p = 0.04), Xrs8 (p = 0.02) and AX (p = 0.01) were found. When stratifying for age, significant difference between measured and predicted values was observed only in children

Naoya Takeichi,1 Haruna Yamazaki,1 Keisaku Fujimoto21Department of Biomedical Laboratory Sciences, Graduate School of Medicine, Shinshu University, Matsumoto, Nagano, Japan; 2Department of Clinical Laboratory Sciences, Shinshu University School of Health Sciences, Matsumoto, Nagano, JapanObjective: To examine whether the parameters of impedance measured by the broadband frequency forced oscillation technique (FOT) were reflected by changes in lung compliance induced by emphysema and fibrosis, we retrospectively compared the parameters of FOT and pulmonary functions, including static lung compliance (Cst), in obstructive lung disease (OLD) and interstitial lung disease (ILD).Patients and methods: The data of 18 patients with OLD (16 with COPD, two with asthma COPD overlap), 11 with ILD, and 24 healthy volunteers, whose respiratory impedance was measured using a MostGraph-01 and other pulmonary functions including Cst and lung resistance (RL) were measured on the same day and were retrospectively collected and compared.Results: The parameters of resistance, reactance, and resonant frequency showed good correlations with ventilation unevenness (r=0.63, −0.89, 0.77, respectively) and lung elastic resistance (r=0.59, −0.80, 0.73, respectively) in all groups (N=53). These indices were significant determinants of increased respiratory resistance and more negative shift of respiratory reactance (Xrs) at lower frequency (P

Abstract Background Hyperoxia-induced bronchopulmonary dysplasia (BPD) models are essential for better understanding and impacting on long-term pulmonary, cardiovascular, and neurological sequelae of this chronic disease. Only few experimental studies have systematically compared structural alterations with lung function measurements. Methods In three separate and consecutive series, Sprague–Dawley infant rats were exposed from day of life (DOL) 1 to 19 to either room air (0.21; controls) or to fractions of inspired oxygen (FiO2) of 0.6, 0.8, and 1.0. Our primary outcome parameters were histopathologic analyses of heart, lungs, and respiratory system mechanics, assessed via image analysis tools and the forced oscillation technique, respectively. Results Exposure to FiO2 of 0.8 and 1.0 resulted in significantly lower body weights and elevated coefficients of lung tissue damping (G) and elastance (H) when compared with controls. Hysteresivity (η) was lower due to a more pronounced increase of H when compared with G. A positive structure–function relation was demonstrated between H and the lung parenchymal content of α-smooth muscle actin (α-SMA) under hyperoxic conditions. Moreover, histology and morphometric analyses revealed alveolar simplification, fewer pulmonary arterioles, increased α-SMA content in pulmonary vessels, and right heart hypertrophy following hyperoxia. Also, in comparison to controls, hyperoxia resulted in significantly lower plasma levels of vascular endothelial growth factor (VEGF). Lastly, rats in hyperoxia showed hyperactive and a more explorative behaviour. Conclusions Our in vivo infant rat model mimics clinical key features of BPD. To the best of our knowledge, this is the first BPD rat model demonstrating an association between lung structure and function. Moreover, we provide additional evidence that infant rats subjected to hyperoxia develop rarefaction of pulmonary vessels, augmented vascular α-SMA, and adaptive cardiac hypertrophy. Thus, our model provides a clinically relevant tool to further investigate diseases related to O2 toxicity and to evaluate novel pharmacological treatment strategies.

The forced oscillation technique (FOT) is a non-volitional assessment that is used during tidal breathing. A variant of FOT uses a pseudorandom noise (PRN) signal which we postulated might have utility in assessing lung function in prematurely born children. We, therefore, undertook a systematic review to evaluate the evidence regarding PRN FOT. A comprehensive search of the literature was conducted by using the following databases: Medline, Embase, Web of Science and CINAHL. Observational studies, case series/reports and randomized-controlled trials were eligible for inclusion. Article abstracts and full texts were screened independently by two reviewers, with disagreements resolved by discussion or a third reviewer if necessary. Five studies were included (n = 587 preterm children). Three compared PRN FOT with spirometry, and two compare it to the interrupter technique. Most studies failed to report comprehensive methodology of the frequency spectra used to generate the PRN signal. There was evidence that poorer lung function, as assessed by PRN FOT, was associated with a greater burden of respiratory symptoms, but there was insufficient evidence to determine whether PRN FOT performed better than other lung-function tests. Detailed methodological documentation, in accordance with ERS guidance, is needed to assess the benefits of PRN FOT prior to routine clinical incorporation to assess prematurely born children.

Background and objective: Asthma guidelines emphasize the importance of assessing lung function and symptoms. The forced oscillation technique (FOT) and its longitudinal relationship with spirometry and symptoms are unresolved. We examined concordance between longitudinal spirometry, FOT and symptom control, and determined FOT limits of agreement in stable asthma. Methods: Over a 3‐year period, adults with asthma attending a tertiary clinic completed the asthma control test (ACT), fraction of exhaled nitric oxide (FeNO), FOT and spirometry. Analysis included between‐visit concordance for significant change using Cohen's kappa (κ) and stable asthma FOT limits of agreement. Results: Data (n = 186) from 855 visits (mean ± SD 4.6 ± 3.0 visits), 114 ± 95 days apart, were analysed. Between‐visit concordance was moderate between reactance at 5 Hz (X5) and forced expiratory volume in 1 s (FEV1) (κ = 0.34, p = 0.001), and weak between ACT and FEV1 (κ = 0.18, p = 0.001). Change in FeNO did not correlate with lung function or ACT (κ < 0.05, p > 0.1). Stable asthma between visits (n = 75; 132 visits) had reduced lung function variability, but comparable concordance to the entire cohort. Limits of agreement for FEV1 (0.42 L), resistance at 5 Hz (2.06 cm H2O s L−1) and X5 (2.75 cm H2O s L−1) in stable asthma were at least twofold greater than published values in health. Conclusion: In adults with asthma, there is moderate concordance between longitudinal change in FOT and spirometry. Both tests relate poorly to changes in asthma control, highlighting the need for multi‐modal assessment in asthma rather than symptoms alone. The derivation of longitudinal FOT limits of agreement will assist in its clinical interpretation. [ABSTRACT FROM AUTHOR]

Airway oscillometry has become the de facto standard for quality assessment of lung physiology in laboratory animals and has demonstrated its usefulness in understanding diseases of small airways. Nowadays, it is seeing extensive use in daily clinical practice and research; however, a question that remains unanswered is how well physiological findings in animals and humans correlate? Methodological and device differences are obvious between animal and human studies. However, all devices deliver an oscillated airflow test signal and output respiratory impedance. In addition, despite analysis differences, there are ways to interpret animal and human oscillometry data to allow suitable comparisons. The potential with oscillometry is its ability to reveal universal features of the respiratory system across species, making translational extrapolation likely to be predictive. This means that oscillometry can thus help determine if an animal model displays the same physiological characteristics as the human disease. Perhaps more importantly, it can also be useful to determine whether an intervention is effective as well as to understand if it affects the desired region of the respiratory system, e.g., the periphery of the lung. Finally, findings in humans can also inform preclinical scientists and give indications as to what type of physiological changes should be observed in animal models to make them relevant as models of human disease. The present article will attempt to demonstrate the potential of oscillometry in respiratory research, an area where the development of novel therapies is plagued with a failure rate higher than in other disease areas. [ABSTRACT FROM AUTHOR]

Background: Lung function testing is recommended for the management of asthma. Due to certain limitations of conventional spirometry in vulnerable patients, forced oscillation technique (FOT) has been studied with promising results. As there is a paucity of data from developing world, we planned to conduct this study in children using FOT. To assess airway reversibility after inhaled salbutamol in asymptomatic children with suspected asthma. Settings: This study was conducted at pediatric asthma clinic of a tertiary care referral hospital in North India. Design: This was a prospective interventional study over 1‑year period. Subjects and Methods: Asymptomatic children between 2 and 18 years of age, with history suggestive of asthma, were eligible for participation. Baseline and postbronchodilator pulmonary functions were assessed using FOT. Airway resistance and reactance were monitored at various frequencies. SPSS version 17 was used for statistical analysis. Results: Among the 345 enrolled children, baseline mean ± standard deviation total airway resistance (R5 ), central airway resistance (R19), peripheral airway resistance (R5 –R19), reactance (X5 ), and resonant frequency (Fres) were 6.85 ± 2.60, 5.23 ± 1.93, 1.6 ± 1.16, and − 2.54 ± 1.36 cmH2 O/L/s and 17.28 ± 3.06 Hz. The median (interquartile range) percentage change after inhaled salbutamol was 19.9 (11.40, 29.12), 22.86 (6.88, 38.76), 14.08 (3.40, 22.62), 39.20 (8.20, 62.39), and 15.79 (8.33, 27.27) in respective parameters. All changes were statistically significant. The studied respiratory variables were in maximum negative correlation with height, followed by body mass index. Conclusions: FOT is a simple technique for monitoring lung functions in children during asthma management. [ABSTRACT FROM AUTHOR]

Closing volume (CV) is commonly measured by single-breath nitrogen washout (CVSBW). A method based on the forced oscillation technique was recently introduced to detect a surrogate CV (CVFOT). As the two approaches are based on different physiological mechanisms, we aim to investigate CVFOT and CVSBW relationship at different degrees and patterns of airway obstruction. A mathematical model was developed to evaluate the CVSBW and CVFOT sensitivity to different patterns of airway obstruction, either located in a specific lung region or equally distributed throughout the lung. The two CVs were also assessed during slow vital capacity (VC) maneuvers in triplicate in 13 healthy subjects and pre- and postmethacholine challenge (Mch) in 12 subjects with mild-moderate asthma. Model simulations suggest that CVSBW is more sensitive than CVFOT to the presence of few flow-limited or closed airways that modify the contribution of tracer-poor and tracer-rich lung regions to the overall exhaled gas. Conversely, CVFOT occurs only when at least 65% of lung units are flow limited or closed, regardless of their regional distribution. CVSBW did not differ between healthy subjects and those with asthma (17 ± 9% VC vs. 22 ± 10% VC), whereas CVFOT did (16 ± 5% VC vs. 23 ± 6% VC, P < 0.01). In patients with asthma, both CVSBW and CVFOT increased post-Mch (33 ± 7% VC P < 0.001 and 43 ± 12% VC P < 0.001, respectively). CVSBW weakly correlated with CVFOT (r = 0.45, P < 0.01). The closing capacities (CV þ residual volume) were correlated (r = 0.74, P < 0.001), but the changes with Mch in both CVs and closing capacities did not correlate. CVFOT is easy to measure and provides a reproducible parameter useful for describing airway impairment in obstructive respiratory diseases. [ABSTRACT FROM AUTHOR]

Introduction: The use of machine learning (ML) methods would improve the diagnosis of respiratory changes in systemic sclerosis (SSc). This paper evaluates the performance of several ML algorithms associated with the respiratory oscillometry analysis to aid in the diagnostic of respiratory changes in SSc. We also find out the best configuration for this task.Methods: Oscillometric and spirometric exams were performed in 82 individuals, including controls (n = 30) and patients with systemic sclerosis with normal (n = 22) and abnormal (n = 30) spirometry. Multiple instance classifiers and different supervised machine learning techniques were investigated, including k-Nearest Neighbors (KNN), Random Forests (RF), AdaBoost with decision trees (ADAB), and Extreme Gradient Boosting (XGB).Results and Discussion: The first experiment of this study showed that the best oscillometric parameter (BOP) was dynamic compliance, which provided moderate accuracy (AUC = 0.77) in the scenario control group versus patients with sclerosis and normal spirometry (CGvsPSNS). In the scenario control group versus patients with sclerosis and altered spirometry (CGvsPSAS), the BOP obtained high accuracy (AUC = 0.94). In the second experiment, the ML techniques were used. In CGvsPSNS, KNN achieved the best result (AUC = 0.90), significantly improving the accuracy in comparison with the BOP (p < 0.01), while in CGvsPSAS, RF obtained the best results (AUC = 0.97), also significantly improving the diagnostic accuracy (p < 0.05). In the third, fourth, fifth, and sixth experiments, different feature selection techniques allowed us to spot the best oscillometric parameters. They resulted in a small increase in diagnostic accuracy in CGvsPSNS (respectively, 0.87, 0.86, 0.82, and 0.84), while in the CGvsPSAS, the best classifier's performance remained the same (AUC = 0.97).Conclusions: Oscillometric principles combined with machine learning algorithms provide a new method for diagnosing respiratory changes in patients with systemic sclerosis. The present study's findings provide evidence that this combination may help in the early diagnosis of respiratory changes in these patients. [ABSTRACT FROM AUTHOR]

Objectives: Forced oscillation technique (FOT) is becoming increasingly widespread measurement method used for assessment of lung function. In the present study, we attempted to assess FOT values in patients after lobectomy in comparison with IPF and COPD patients. Methods: Twenty‐two patients after lobectomy due to lung cancer stage I or II, 28 patients with idiopathic pulmonary fibrosis and 17 patients with chronic obstructive pulmonary disease were enrolled in the study. All patients performed spirometry (FEV1, FVC, FEV1/FVC, MEF50, MEF25, FEF25‐75, MIF50), plethysmography (Raw, TLC, RV, RV/TLC) and a test using the forced oscillation technique‐ resistance (R at 5Hz, 11Hz and 19Hz, inspiratory, expiratory and total), reactance (Xat 5Hz, 11Hz, inspiratory, expiratory and total), Fres and expiratory flow limitation (∆X). The ANOVA Kruskal‐Wallis test followed by a multiple comparison test were used to evaluate the differences in oscillatory parameters between‐groups. Results: Patients after lobectomy presented reduced X5, X11 and moderately increased R5, R11, R19, R5‐19, ∆X and Fres. Rinsp5 weresignificantly higher when compared with IPF patients (P = 0.001). In lobectomy patients R5, X5, X11, ∆X and Fres were significantly less affected when compared with patients with COPD (P < 0.05 for all values). R5‐19, which reflects small airways dysfunction, occurred to be similarly elevated as in COPD patients (0.5 vs 0.6 cmH2O/L/s).Abnormalities of reactance at 11Hz were observed more frequently than at 5Hz in all groups of patients. Conclusion: Patients after lobectomy due to lung cancer presented FOT abnormalities, which could be caused by lung parenchymal abnormalities following recent thoracic surgery. [ABSTRACT FROM AUTHOR]

BACKGROUND: A 20% reduction in the FEV1 is routinely used as an end point for methacholine challenge testing (MCT). Measurement of FEV1 is effort dependent, and some patients are not able to perform acceptable and repeatable forced expiration maneuvers. The goal of the present study was to investigate the diagnostic value of airway resistance measurement by forced oscillation technique (FOT), body plethysmography, and interrupter technique compared with the traditionally accepted standard FEV1 measurement in evaluating the responsiveness to methacholine during MCT. METHODS: We included in the study adult subjects referred for MCT because of asthma-like symptoms and with normal baseline spirometry. We modified routine MCT protocol by adding the assessment of airway resistance to the measurement of FEV1 at each step of MCT. RESULTS: We observed, in the subjects with airway hyper-responsiveness versus those with normal airway responsiveness, a significantly greater percentage change in median (interquartile range) FOT resistance at 10 Hz (25.9% [13.7%-35.4%] vs 16% [15.7%-27.2%]), plethysmographic resistance (70.2% [39.5%-116.3%] vs 37.1% [23.9%-81.9%]), and mean 6 SD conductance (241.3 6 15.4% vs 229.6 6 15.9%); and a significantly greater change in mean 6 SD FOT reactance at 10 Hz (-0.41 6 0.48 cm H2O/L/s vs -0.09 6 0.32 cm H2O/L/s) and at 15 Hz (-0.29 6 0.2 cm H2O/L/s vs -0.1 6 0.19 cm H2O/L/s). We also recorded significant differences in airway resistance parameters (FOT resistance at 10 Hz, FOT reactance at 15 Hz, plethysmographic airway resistance, and conductance indices as well as interrupter resistance) in FEV1 non-responders at the onset of respiratory symptoms during MCT compared with baseline. CONCLUSIONS: Measurements of airway resistance could possibly be used as an alternative method to spirometry in airway challenge. Significant changes in airway mechanics during MCT are detectable by airway resistance measurement in FEV1 non-responders with methacholine-induced asthma-like symptoms. (ClinicalTrials.gov registration NCT02343419.) [ABSTRACT FROM AUTHOR]

OBJECTIVE: The present study was aimed to evaluate the diagnostic accuracy of impedance parameters to detect airflow obstruction and the severity of airflow obstruction in adults. METHODS: The spirometry parameters (forced expiratory volume in 1 s [FEV1], forced vital capacity [FVC], FEV1/FVC, FVC3/FVC, and FEF25-75) and respiratory impedance parameters (R5, R19, R5-19, and X5) measured by forced oscillation technique of consecutive 299 adults (male: 186) were included in the present analysis. The Spearman correlation coefficient (ρ) was used to assess the correlations of impedance parameters with spirometry indices. The area under the curve (AUC) was used to assess respiratory impedance parameters' diagnostic accuracy. RESULTS: The mean age of the study population was 54.1 ± 12.3 years, and 99 individuals (33%) had airflow obstruction (FEV1/FVC < 0.70) in spirometry. All spirometry indices (% of predicted) showed a weak negative correlation with R5, R19, R5-19, and weak positive correlation with X5. The R5 >142% predicted and X5 >136% predicted had the maximum AUC (0.75) with a sensitivity of up to 56% and specificity up to 86% to identify airflow obstruction. The impedance parameters showed low concordance with the severity of airflow obstruction. CONCLUSION: Respiratory impedance parameters had insufficient sensitivity to diagnose airflow obstruction and the severity of obstruction in adults. Thus, impedance parameters cannot a substitute for spirometry in diagnosing obstructive lung function. [ABSTRACT FROM AUTHOR]

Abstract Many studies have reported reference data for forced oscillation technique (FOT) in healthy children. The prediction equation of FOT parameters were derived from a multivariable regression model examining the effect of age, gender, weight and height on each parameter. As many of these variables are likely to be correlated, collinearity might have affected the accuracy of the model, potentially resulting in misleading, erroneous or difficult to interpret conclusions. The aim of this work was: To review all FOT publications in children since 2005 to analyze whether collinearity was considered in the construction of the published prediction equations. Then to compare these prediction equations with our own study. And to analyse, in our study, how collinearity between the explanatory variables might affect the predicted equations if it was not considered in the model. The results showed that none of the ten reviewed studies had stated whether collinearity was checked for. Half of the reports had also included in their equations variables which are physiologically correlated, such as age, weight and height. The predicted resistance varied by up to 28% amongst these studies. And in our study, multicollinearity was identified between the explanatory variables initially considered for the regression model (age, weight and height). Ignoring it would have resulted in inaccuracies in the coefficients of the equation, their signs (positive or negative), their 95% confidence intervals, their significance level and the model goodness of fit. In Conclusion with inaccurately constructed and improperly reported models, understanding the results and reproducing the models for future research might be compromised.

Background: Fractional-order (FrOr) models have a high potential to improve pulmonary science. These models could be useful for biomechanical studies and diagnostic purposes, offering accurate models with an improved ability to describe nature. This paper evaluates the performance of the Forced Oscillation (FO) associated with integer (InOr) and FrOr models in the analysis of respiratory alterations in work-related asthma (WRA).Methods: Sixty-two individuals were evaluated: 31 healthy and 31 with WRA with mild obstruction. Patients were analyzed pre- and post-bronchodilation. The diagnostic accuracy was evaluated using the area under the receiver operating characteristic curve (AUC). To evaluate how well do the studied models correspond to observed data, we analyzed the mean square root of the sum (MSEt) and the relative distance (Rd) of the estimated model values to the measured resistance and reactance measured values.Results and Discussion: Initially, the use of InOr and FrOr models increased our understanding of the WRA physiopathology, showing increased peripheral resistance, damping, and hysteresivity. The FrOr model (AUC = 0.970) outperformed standard FO (AUC = 0.929), as well as InOr modeling (AUC = 0.838) in the diagnosis of respiratory changes, achieving high accuracy. FrOr improved the curve fitting (MSEt = 0.156 ± 0.340; Rd = 3.026 ± 1.072) in comparison with the InOr model (MSEt = 0.367 ± 0.991; Rd = 3.363 ± 1.098). Finally, we demonstrated that bronchodilator use increased dynamic compliance, as well as reduced damping and peripheral resistance.Conclusions: Taken together, these results show clear evidence of the utility of FO associated with fractional-order modeling in patients with WRA, improving our knowledge of the biomechanical abnormalities and the diagnostic accuracy in this disease. [ABSTRACT FROM AUTHOR]

Quantile regression is widely used to estimate conditional quantiles of an outcome variable of interest given covariates. This method can estimate one quantile at a time without imposing any constraints on the quantile process other than the linear combination of covariates and parameters specified by the regression model. While this is a flexible modeling tool, it generally yields erratic estimates of conditional quantiles and regression coefficients. Recently, parametric models for the regression coefficients have been proposed that can help balance bias and sampling variability. So far, however, only models that are linear in the parameters and covariates have been explored. This paper presents the general case of nonlinear parametric quantile models. These can be nonlinear with respect to the parameters, the covariates, or both. Some important features and asymptotic properties of the proposed estimator are described, and its finite-sample behavior is assessed in a simulation study. Nonlinear parametric quantile models are applied to estimate extreme quantiles of longitudinal measures of respiratory mechanics in asthmatic children from an epidemiological study and to evaluate a dose–response relationship in a toxicological laboratory experiment. [ABSTRACT FROM AUTHOR]

Introduction: Bronchial asthma (BA) and obstructive sleep apnea syndrome (OSAS) are common causes of respiratory disturbance. Many cases of patients with both conditions have been reported, and BA and OSAS may exacerbate each other, but information remains sparse. Methods:We retrospectively evaluated 60 patients under treatment for BA in our department between April 2016 and March 2018 who also underwent portable polysomnography (PSG) for suspected OSAS to assess potential association between PSG results and asthma treatment or respiratory function. BA was diagnosed and treated according to the Asthma Prevention and Management Guideline 2015. Results: We found that BA treatment intensity step was significantly higher for patients with BA who had concurrent moderate or severe OSAS (p = 0.0016). However, neither respiratory function, fraction of exhaled nitric oxide (FeNO), nor forced oscillation technique (FOT) differed significantly between patients with and without OSAS, and apnea hypopnea index was not significantly correlated with respiratory function, FeNO or FOT parameters. Conclusion:We conclude that even though BA patients with OSAS had good respiratory function, their BA was more severe than that of patients without OSAS, suggesting that OSAS may exacerbate BA. Background factors and asthma parameters were not predictive of PSG results, and patients with suspected OSAS should be evaluated proactively by using PSG. [ABSTRACT FROM AUTHOR]

To design machine learning classifiers to facilitate the clinical use and increase the accuracy of the forced oscillation technique (FOT) in the differential diagnosis of patients with asthma and restrictive respiratory diseases. FOT and spirometric exams were performed in 97 individuals, including controls (n = 20), asthmatic patients (n = 38), and restrictive (n = 39) patients. The first experiment of this study showed that the best FOT parameter was the resonance frequency, providing moderate accuracy (AUC = 0.87). In the second experiment, a neuro-fuzzy classifier and different supervised machine learning techniques were investigated, including k-nearest neighbors, random forests, AdaBoost with decision trees, and support vector machines with a radial basis kernel. All classifiers achieved high accuracy (AUC ≥ 0.9) in the differentiation between patient groups. In the third and fourth experiments, the use of different feature selection techniques allowed us to achieve high accuracy with only three FOT parameters. In addition, the neuro-fuzzy classifier also provided rules to explain the classification. Neuro-fuzzy and machine learning classifiers can aid in the differential diagnosis of patients with asthma and restrictive respiratory diseases. They can assist clinicians as a support system providing accurate diagnostic options. [ABSTRACT FROM AUTHOR]

Purpose: Previous studies revealed substantially varying therapy efficacy of automatic continuous positive airway pressure (APAP) devices in the treatment of obstructive sleep apnea (OSA). We evaluated the efficacy of a new APAP device using the forced oscillation technique (FOT) to evaluate upper airway obstruction during apneas and flow contour analyses during hypopneas. Methods: Forty-six initially diagnosed OSA patients were included and the pressure range was set from 5 to 20 hPa. Therapy efficacy was assessed based on the reduction of apnea-hypopnea index (AHI), improvement of objective sleep quality parameters, and the appropriateness of the device's pressure regulation. Results: AHI and arousal index significantly decreased during APAP therapy (median [interquartile range]: AHI 36 [23–55] vs. 2 [1–6]/h, arousal index 30 [22–45] vs. 15 [10–19]/h, both p < 0.001). The amount of slow wave sleep (SWS) and rapid-eye-movement (REM) sleep significantly increased (SWS 20 [14–29] vs. 29 [19–34]%, REM 16 [11–21] vs. 24 [14–30]%, both p < 0.01). Most residual respiratory events during therapy were of central etiology and attributable to five patients, who presented with treatment-emergent central sleep apnea. The device's pressure regulation abolished most obstructive respiratory events (n = 6.7 residual obstructive events per patient). Of central respiratory events, 534/646 (83%) did not lead to pressure increases. Conclusion: This pilot study provides a proof of concept that the APAP device combining FOT and evaluation of flow contour allows for the suppression of obstructive events without relevant false reactions. [ABSTRACT FROM AUTHOR]

Background and objective: Abnormal peripheral airway function is an important feature of asthma and relates to asthma symptoms and poor asthma control. We aimed to determine whether peripheral airway function, as measured by forced oscillatory impedance and multiple‐breath nitrogen washout (MBNW), relates to symptom improvement in asthmatic participants with uncontrolled asthma, after stepping up to high‐dose ICS/LABA treatment. Methods: A total of 19 subjects (14 females, mean age: 29.9 ± 13.6 years) with uncontrolled asthma, as defined by an ACQ5 > 1.5, taking 500 μg/day fluticasone equivalent or less, underwent spirometry, plethysmography, fractional exhaled FeNO, forced oscillatory resistance (Rrs5Hz) and reactance (Xrs5Hz), and indices of MBNW ventilation heterogeneity (lung clearance index (LCI), diffusion‐convection‐dependent (Sacin) and convection‐dependent (Scond)). Measurements were made before and after 8 weeks of treatment with fluticasone/formoterol combination inhaler 250/10 μg, 2 puffs twice daily. Results: Treatment improved ACQ5 (P = 0.0002), FEV1 (P = 0.02), FVC (P = 0.04), FeNO (P = 0.0008), Xrs5Hz (P = 0.01), LCI (P = 0.0002), Sacin (P = 0.006) and Scond (P = 0.01). At baseline, ACQ5 correlated with Xrs5Hz (rs = 0.52, P = 0.03) and Rrs5Hz (rs = 0.55, P = 0.02). The improvement in ACQ5 was predicted by more abnormal baseline LCI (P = 0.03), Scond (P = 0.02) and Rrs5Hz (P = 0.006). Baseline Scond was the best predictor of a clinically meaningful improvement in asthma control (ΔACQ > 0.5, ROC‐AUC = 0.91, P = 0.007). Conclusion: Step‐up to high‐dose combination treatment in uncontrolled asthma is associated with improved peripheral airway function as measured by Xrs5Hz and MBNW. Baseline MBNW and FOT parameters correlated with the improvement in symptoms and may predict a positive response to up‐titration in uncontrolled asthmatic patients. [ABSTRACT FROM AUTHOR]

Background: Persistent bronchodilator response (BDR) following diagnosis of asthma is an underrecognized treatable trait, associated with worse lung function and asthma control. The forced oscillation technique (FOT) measures respiratory system impedance, and BDR cutoffs have been proposed for healthy adults; however, the relevance in asthma is unknown. We compared BDR cutoffs, using FOT and spirometry, in asthma and the relationship with asthma control.Methods: Data from patients with asthma who withheld bronchodilator medication for at least 8 h before a tertiary airway clinic visit were reviewed. All subjects performed FOT and spirometry before and after salbutamol administration, and completed the Asthma Control Test. FOT parameters examined included respiratory system resistance (R5) and reactance (X5) at 5 Hz, and area under the reactance curve (AX). BDR was defined by standard recommendations for spirometry and based on the 95th percentile of BDR in healthy adults for FOT.Results: Fifty-two subjects (18 men; mean age, 53 ± 18 years) were included. BDR was identified more frequently by FOT than spirometry (54% vs 27% of subjects). BDR assessed by X5 and AX, but not R5, was associated with spirometric BDR (χ2, P < .01) and correlated with asthma control (X5: rs = -0.36, P < .01; AX: rs = 0.34, P = .01). BDR measured by reactance parameters identified more subjects with poor asthma control than did spirometry (AX, 69% vs spirometry, 41%).Conclusions: BDR assessed by FOT can identify poor asthma control. Reactance parameters were more sensitive in identifying poor asthma control than spirometry, supporting the use of FOT to complement spirometry in the clinical management of asthma. [ABSTRACT FROM AUTHOR]

Despite recent insights into the dynamic processes during lung aeration at birth, several aspects remain poorly understood. We aimed to characterize changes in lung mechanics during the first inflation at birth and their relationship to changes in lung volume. Intubated preterm lambs (gestational age, 124–127 days; n = 17) were studied at birth. Lung volume changes were measured by electrical impedance tomography (VLEIT). Respiratory system resistance (R5) and oscillatory compliance (Cx5) were monitored with the forced oscillation technique at 5 Hz. Lambs received 3–7 s of 8 cmH2O of continuous distending pressure (CDP) before delivery of a sustained inflation (SI) of 40 cmH2O. The SI was then applied until either Cx5 or the VLEIT or the airway opening volume was stable. CDP was resumed for 3–7 s before commencement of mechanical ventilation. The exponential increases with time of Cx5 and VLEIT from commencement of the SI were characterized by estimating their time constants (τCx5 and τVLEIT, respectively). During SI, a fast decrease in R5 and an exponential increase in Cx5 and VLEIT were observed. Cx5 and VLEIT provided comparable information on the dynamics of lung aeration in all lambs, with τCx5 and τVLEIT being highly linearly correlated (r2 = 0.87, P < 0.001). Cx5 and VLEIT decreased immediately after SI. Despite the standardization of the animal model, changes in Cx5 and R5 both during and after SI were highly variable. Lung aeration at birth is characterized by a fast reduction in resistance and a slower increase in oscillatory compliance, the latter being a direct reflection of the amount of lung aeration. [ABSTRACT FROM AUTHOR]

Objective: To develop regression equations of within and whole-breath respiratory impedance for Indian children aged 5 to 17 y.Methods: A prospective cross-sectional study was carried out in 5 to 17 y old school children of Bhopal, India. Healthy children were identified by physical examination and by administering questionnaire. The respiratory system resistance (Rrs) and reactance (Xrs) were measured at frequency of 5, 11, and 19 Hz by forced oscillation technique (FOT). The regression equations of within and whole-breath Rrs and Xrs were developed separately for boys and girls by multiple linear regression models.Results: Total 336 children were recruited and data of 320 healthy children (boys - 159), standing height of 146.1 ± 16.6 cm and body mass index of 17.2 ± 2.9 kg/m2 were included in the analysis. The mean respiratory system resistance at 5 Hz (R5) and respiratory system reactance at 5 Hz (X5) of the children, irrespective of gender were 5.46 ± 2.10 cmH2O/L/s and - 1.43 ± 0.85 cmH2O/L/s respectively. Boys of age 16 y and older had significantly smaller Rrs as compared to girls of corresponding age (p < 0.05). The standing height of children had the highest predictive power, followed by age in the regression model. With an increase in standing height, the magnitude of both Rrs and Xrs values of children decrease. The bodyweight of children had a negligible contribution to the regression models.Conclusions: The regression equations of within- and whole-breath Rrs and Xrs of Indian children aged 5 to 17 y are presented for the first time. The R5 values of Indian children were comparable to children of other ethnicities. [ABSTRACT FROM AUTHOR]

Background: Bronchial Thermoplasty (BT) is an endoscopic treatment for severe asthma using radiofrequency energy to target airway remodeling including smooth muscle. The correlation of pulmonary function tests and BT response are largely unknown. Forced Oscillation Technique (FOT) is an effort-independent technique to assess respiratory resistance (Rrs) by using pressure oscillations including small airways.Aim: To investigate the effect of BT on pulmonary function, assessed by spirometry, bodyplethysmography and FOT and explore associations between pulmonary function parameters and BT treatment response.Methods: Severe asthma patients recruited to the TASMA trial were analyzed in this observational cohort study. Spirometry, bodyplethysmography and FOT measurements were performed before and 6 months after BT. Asthma questionnaires (AQLQ/ACQ-6) were used to assess treatment response.Results: Twenty-four patients were analyzed. AQLQ and ACQ improved significantly 6 months after BT (AQLQ 4.15 (±0.96) to 4.90 (±1.14) and ACQ 2.64 (±0.60) to 2.11 (±1.04), p = 0.004 and p = 0.02 respectively). Pulmonary function parameters remained stable. Improvement in FEV1 correlated with AQLQ change (r = 0.45 p = 0.03). Lower respiratory resistance (Rrs) at baseline (both 5 Hz and 19 Hz) significantly correlated to AQLQ improvement (r = - 0.52 and r = - 0.53 respectively, p = 0.01 (both)). Borderline significant correlations with ACQ improvement were found (r = 0.30 p = 0.16 for 5 Hz and r = 0.41 p = 0.05 for 19 Hz).Conclusion: Pulmonary function remained stable after BT. Improvement in FEV1 correlated with asthma questionnaires improvement including AQLQ. Lower FOT-measured respiratory resistance at baseline was associated with favorable BT response, which might reflect targeting of larger airways with BT.Trial Registration: ClinicalTrials.gov Identifier: NCT02225392; Registered 26 August 2014. [ABSTRACT FROM AUTHOR]

Background: Forced oscillation technique (FOT) is a technique to measure the mechanical properties of the lung. The present study was aimed to develop regression equations of within- and whole-breath respiratory impedance (Zrs) of healthy Indian adults. Methods: Total 323 adults were sequentially screened. Smokers, individuals with respiratory symptoms or diseases, and unable to perform acceptable FOT were excluded. Within- and whole-breath resistance (Rrs) and reactance (Xrs) were measured at 5, 11, and 19 Hz by Resmon Pro® Full device. The regression equations of within- and whole-breath Rrs and Xrs were generated separately for men and women by multiple linear regression models. Results: The FOT data of 253 individuals (122 men) aged 18–81 years were included in the analysis. The magnitudes of whole-breath Rrs at 5 Hz (4.53 ± 1.05 cmH2O/L/s in women vs. 3.26 ± 1.05 cmH2O/L/s in men; P = 0.000) and whole-breath Xrs at 5 Hz (−1.23 ± 0.66 cmH2O/L/s in women vs. −1.00 ± 0.54 cmH2O/L/s in men; P = 0.003) of women were significantly of higher magnitude as compared to men. The standing height was the best determinant of Zrs, followed by body weight; the effect of age was negligible and was observed in men only. The magnitudes of both Rrs and Xrs decrease with an increase in standing height of both men and women. Conclusions: The present study provides regression equations of within- and whole-breath respiratory impedance of Indian adults. [ABSTRACT FROM AUTHOR]

High-frequency oscillatory ventilation (HFOV) is a type of mechanical ventilation with a protective potential characterized by a small tidal volume. Unfortunately, HFOV has limited monitoring of ventilation parameters and mechanical parameters of the respiratory system, which makes it difficult to adjust the continuous distension pressure (CDP) according to the individual patient’s airway status. Airway resistance Raw is one of the important parameters describing the mechanics of the respiratory system. The aim of the presented study was to verify in vitro whether the resistance of the respiratory system Rrs can be reliably determined during HFOV to evaluate Raw in pediatric and adult patients. An experiment was performed with a 3100B high-frequency oscillator, a physical model of the respiratory system, and a pressure and flow measurement system. The physical model with different combinations of resistance and compliance was ventilated during the experiment. The resistance Rrs was calculated from the impedance of the physical model, which was determined from the spectral density of the pressure at airway opening and the spectral cross-density of the gas flow and pressure at airway opening. Rrs of the model increased with an added resistor and did not change significantly with a change in compliance. The method is feasible for monitoring respiratory system resistance during HFOV and has the potential to optimize CDP settings during HFOV in clinical practice.

Anti-tumor necrosis factor alpha (TNFα) therapy is widely used to treat various inflammatory conditions. Paradoxically, there are several case reports describing the development of bronchocentric granulomatosis treated with TNFα inhibitors, and it is difficult to determine the effect of treatment using conventional spirometry because the lesions are located in small airways. However, it has been reported that the forced oscillation technique (FOT) is useful in the evaluation of small airway disease in bronchial asthma or chronic obstructive pulmonary disease. We performed the FOT to determine the effect of treatment on bronchocentric granulomatosis and found it to be useful. We report the case of a 55-year-old female with ulcerative colitis who was treated with golimumab and who developed bronchocentric granulomatosis as a sarcoid-like reaction to golimumab. She was successfully treated with prednisone, and the treatment efficacy was confirmed by the FOT. The FOT may be useful in the evaluation of small airway disease in bronchocentric granulomatosis. This case may help inform clinicians of the usefulness of the FOT to assess small airway disease in various diseases.

Hitomi Yamagami, Akihiko Tanaka, Yasunari Kishino, Hatsuko Mikuni, Tomoko Kawahara, Shin Ohta, Mayumi Yamamoto, Shintaro Suzuki, Tsukasa Ohnishi, Hironori Sagara Division of Respiratory Medicine and Allergology, Department of Medicine, School of Medicine, Showa University, Tokyo, Japan Background: It is well known that increased airflow limitation as measured by spirometry is associated with the risk of exacerbation in patients with COPD. The forced oscillation technique (FOT) is a noninvasive method used to assess respiratory impedance (resistance and reactance) with minimal patient cooperation required. The clinical utility of the FOT in assessing the risk of exacerbations of COPD is yet to be determined. We examined the relationship between respiratory impedance as measured by FOT and exacerbations in patients with COPD. Materials and methods: Among 310 patients with COPD (Global Initiative for Chronic Obstructive Lung Disease stages I–IV) who presented at the outpatient clinic of the Showa University Hospital from September 2014 through January 2015, 119 were collected and assigned into 2 groups according to their history of exacerbation: exacerbators and nonexacerbators. Respiratory resistance components and respiratory reactance components, as measured by FOT, were compared between the two groups. Results: Exacerbators were significantly older and had a higher white blood cell count than nonexacerbators. Resistance at 20 Hz, reactance at 5 Hz (X5), resonant frequency (Fres), and area of low reactance (ALX) differed significantly between the two groups. In addition, among patients with stage II COPD, there were significant differences in X5, Fres, and ALX between the two groups despite no significant differences in respiratory function as assessed by spirometry. Finally, receiver operating characteristic curve analysis revealed that the reactance components rather than the resistance components were associated with the risk of exacerbation. Conclusion: There were significant differences in respiratory impedance between exacerbators and nonexacerbators in patients with moderate COPD. FOT is a promising tool for assessing future exacerbations in patients with COPD. Keywords: forced oscillation technique, respiratory system resistance and reactance, spirometry

Shoichiro Yamamoto,1 Seigo Miyoshi,1 Hitoshi Katayama,1 Mikio Okazaki,2 Hisayuki Shigematsu,2 Yoshifumi Sano,2 Minoru Matsubara,3 Naohiko Hamaguchi,1 Takafumi Okura,1 Jitsuo Higaki1 1Department of Cardiology, Pulmonology, Hypertension, and Nephrology, 2Department of Cardiovascular and Thoracic Surgery, Ehime University Graduate School of Medicine, Toon, 3Department of Internal Medicine, Sumitomo Besshi Hospital, Niihama, Japan Purpose: Spirometry is sometimes difficult to perform in elderly patients and in those with severe respiratory distress. The forced-oscillation technique (FOT) is a simple and noninvasive method of measuring respiratory impedance. The aim of this study was to determine if FOT data reflect spirometric indices.Patients and methods: Patients underwent both FOT and spirometry procedures prior to inclusion in development (n=1,089) and validation (n=552) studies. Multivariate linear regression analysis was performed to identify FOT parameters predictive of vital capacity (VC), forced VC (FVC), and forced expiratory volume in 1 second (FEV1). A regression equation was used to calculate estimated VC, FVC, and FEV1. We then determined whether the estimated data reflected spirometric indices. Agreement between actual and estimated spirometry data was assessed by Bland–Altman analysis.Results: Significant correlations were observed between actual and estimated VC, FVC, and FEV1 values (all r>0.8 and P0.8 and P

Bernt Boegvald Aarli,1,2 Peter MA Calverley,3 Robert L Jensen,4 Raffaele Dellacà,5 Tomas ML Eagan,1,2 Per S Bakke,1 Jon A Hardie1 1Department of Clinical Science, University of Bergen, 2Department of Thoracic Medicine, Haukeland University Hospital, Bergen, Norway; 3Clinical Science Centre, University Hospital Aintree, Liverpool, UK; 4LDS Hospital, Pulmonary Division, Salt Lake City, UT, USA; 5TBM-Lab, Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano University, Milano, Italy Background: Tidal expiratory flow limitation (EFLT) is frequently found in patients with COPD and can be detected by forced oscillations when within-breath reactance of a single-breath is ≥0.28 kPa·s·L-1. The present study explored the association of within-breath reactance measured over multiple breaths and EFLT with 6-minute walk distance (6MWD), exacerbations, and mortality.Methods: In 425 patients, spirometry and forced oscillation technique measurements were obtained on eight occasions over 3 years. 6MWD was assessed at baseline and at the 3-year visit. Respiratory symptoms, exacerbations, and hospitalizations were recorded. A total of 5-year mortality statistics were retrieved retrospectively. We grouped patients according to the mean within-breath reactance (ΔXrs), measured over several breaths at baseline, calculated as mean inspiratory–mean expiratory reactance over the sampling period. In addition to the established threshold of EFLT, an upper limit of normal (ULN) was defined using the 97.5th percentile of ΔXrs of the healthy controls in the study; 6MWDs were compared according to ΔXrs, as normal, ≥ ULN < EFLT, or ≥ EFLT. Annual exacerbation rates were analyzed using a negative binomial model in the three groups, supplemented by time to first exacerbation analysis, and dichotomizing patients at the ULN.Results: In patients with COPD and baseline ΔXrs below the ULN (0.09 kPa·s·L-1), 6MWD was stable. 6MWD declined significantly in patients with ΔXrs ≥ ULN. Worse lung function and more exacerbations were found in patients with COPD with ΔXrs ≥ ULN, and patients with ΔXrs ≥ ULN had shorter time to first exacerbation and hospitalization. A significantly higher mortality was found in patients with ΔXrs ≥ ULN and FEV1 >50%.Conclusion: Patients with baseline ΔXrs ≥ ULN had a deterioration in exercise performance, more exacerbations, and greater hospitalizations, and, among those with moderate airway obstruction, a higher mortality. ΔXrs is a novel independent marker of outcome in COPD. Keywords: forced oscillation technique, reactance, COPD, exacerbations, 6-minute walk test, mortality

Takahiro Kamada, Masahiro Kaneko, Hiromi Tomioka Department of Respiratory Medicine, Kobe City Medical Center West Hospital, Kobe, Japan Background: Forced oscillation technique (FOT) has been reported to be useful in the evaluation and management of obstructive lung disease, including COPD. To date, no data are available concerning long-term changes in respiratory system impedance measured by FOT. Additionally, although exacerbations have been reported to be associated with excessive lung function decline in COPD, the impact of exacerbations on the results of FOT has not been demonstrated. The aim of this study was to investigate the longitudinal changes in respiratory system impedance and the influence of exacerbations thereon. Methods: Between March 2011 and March 2012, outpatients who attended Kobe City Medical Center West Hospital with a diagnosis of COPD were assessed for eligibility. Baseline patient characteristics (age, sex, body mass index, smoking history, current smoking status, COPD stage), lung function (post-bronchodilator forced expiratory volume in 1 second [FEV1]), blood tests (neutrophils and eosinophils), FOT, and COPD assessment test results were collected at enrollment. Lung function and FOT were examined every 6 months until March 2016. Annual changes in FEV1 and FOT parameters were obtained from the slope of the linear regression curve. The patients were divided into 2 groups based on exacerbation history. Results: Fifty-one of 58 patients with COPD were enrolled in this study. The median follow-up period was 57 (52–59) months. Twenty-five (49%) patients experienced exacerbations. A significant annual decline in FEV1 and respiratory system impedance were shown. Additionally, annual changes in FEV1, respiratory system resistance at 5 Hz, respiratory system reactance at 5 Hz, and resonant frequency were greater in patients with exacerbations than in those without exacerbations. Conclusion: Exacerbations of COPD lead not only to a decline in lung function but also to an increase in respiratory system impedance. Keywords: chronic obstructive pulmonary disease, forced oscillation technique, lung function tests, respiratory system, impedance, resistance

This paper introduces the use of low frequencies forced oscillation technique (FOT) in the presence of breathing signal. The hypothesis tested is to evaluate the sensitivity of FOT to various degrees of obstruction in COPD patients. The measurements were performed in the frequency range 0–2 Hz. The use of FOT to evaluate respiratory impedance has been broadly recognized and its complementary use next to standardized method as spirometry and body plethysmography has been well-documented. Typical use of FOT uses frequencies between 4–32 Hz and above. However, interesting information at frequencies below 4 Hz is related to viscoelastic properties of parenchyma. Structural changes in COPD affect viscoelastic properties and we propose to investigate the use of FOT at low frequencies with a fourth generation fan-based FOT device. The generator non-linearity introduced by the device is separated from the linear approximation of the impedance before evaluating the results on patients. Three groups of COPD obstruction, GOLD II, III, and IV are evaluated. We found significant differences in mechanical parameters (tissue damping, tissue elasticity, hysteresivity) and increased degrees of non-linear dynamic contributions in the impedance data with increasing degree of obstruction (p < 0.01). The results obtained suggest that the non-linear index correlates better with degrees of heterogeneity linked to COPD GOLD stages, than the currently used hysteresivity index. The protocol and method may prove useful to improve current diagnosis percentages for various COPD phenotypes.

Background: Several factors may influence quality of life (QOL) for patients with primary ciliary dyskinesia (PCD). We aimed to evaluate the association between pulmonary functions, nasal symptoms and QOL in PCD patients., Methods: A prospective single center study. Patients performed spirometry, whole body plethysmography, forced oscillation technique (FOT), lung clearance index (LCI), 6-min walk test (6MWT), and filled two questionnaires: a specific PCD QOL questionnaire (PCD-QOL) and Sino-nasal outcome test (SNOT-22) questionnaire, assessing symptoms of chronic rhinosinusitis and health related QOL., Results: Twenty-seven patients (56% females), age 19.4 ± 10.5 years were included; their, FEV1 was 74.6 ± 22.7%, and RV/TLC was (157.3 ± 39.3% predicted). Health perception and lower respiratory symptoms domains of PCD-QOL had the lowest score (median [IQR]: 50 [33.3-64.6] and 57.1 [38.9-72.2], respectively). FOT parameters correlated with several PCD-QOL domains. R5 z-score (indicating total airway resistance) and AX z-score (indicating airway reactance) correlated negatively with physical domain (r = -0.598, p = .001, and r = -0.42, p = .03, respectively); R5 z-score also correlated negatively with hearing domain (r = -0.57, p = .002). R5-20 z-score (indicating small airway resistance) correlated negatively with role domain (r = -0.49, p = .03). SNOT-22 score correlated negatively with several PCD-QOL domains (lower respiratory symptoms r = -0.77, p < .001; physical r = -0.72, p < .001; upper respiratory symptoms r = -0.66, p < .001). No correlations were found between spirometry values, LCI, 6MWT, and PCD-QOL., Conclusions: FOT suggested small airway dysfunction, and correlated negatively with several PCD-QOL domains. Nasal symptoms had strong negative correlations with PCD-QOL. Larger longitudinal studies will further elucidate factors affecting QOL in PCD., (© 2023 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Bronchodilation alters both respiratory system resistance (Rrs) and reactance (Xrs) in asthma, but how changes in Rrs and Xrs compare, and respond differently in health and asthma, in reflecting the contributions from the large and small airways has not been assessed. We assessed reversibility using spirometry and oscillometry in healthy and asthma subjects. Using a multibranch airway-tree model with the mechanics of upper airway shunt, we compared the effects of airway dilation and small airways recruitment to explain the changes in Rrs and Xrs. Bronchodilator decreased Rrs by 23.0 (19.0)% in 18 asthma subjects and by 13.5 (19.5)% in 18 healthy subjects. Estimated respiratory system elastance (Ers) decreased by 23.2 (21.4)% in asthma, with no significant decrease in healthy subjects. With the use of the model, airway recruitment of 15% across a generation of the small airways could explain the changes in Ers in asthma with no recruitment in healthy subjects. In asthma, recruitment accounted for 40% of the changes in Rrs, with the remaining explained by airway dilation of 6.8% attributable largely to the central airways. Interestingly, the same dilation magnitude explained the changes in Rrs in healthy subjects. Shunt only affected Rrs of the model. Ers was unaltered in health and unaffected by shunt in both groups. In asthma, Ers changed comparably to Rrs and could be attributed to small airways, while the change in Rrs was split between large and small airways. This implies that in asthma Ers sensed through Xrs may be a more effective measure of small airways obstruction and recruitment than Rrs. [ABSTRACT FROM AUTHOR]

This paper introduces the use of low frequencies forced oscillation technique (FOT) in the presence of breathing signal. The hypothesis tested is to evaluate the sensitivity of FOT to various degrees of obstruction in COPD patients. The measurements were performed in the frequency range 0–2 Hz. The use of FOT to evaluate respiratory impedance has been broadly recognized and its complementary use next to standardized method as spirometry and body plethysmography has been well-documented. Typical use of FOT uses frequencies between 4–32 Hz and above. However, interesting information at frequencies below 4 Hz is related to viscoelastic properties of parenchyma. Structural changes in COPD affect viscoelastic properties and we propose to investigate the use of FOT at low frequencies with a fourth generation fan-based FOT device. The generator non-linearity introduced by the device is separated from the linear approximation of the impedance before evaluating the results on patients. Three groups of COPD obstruction, GOLD II, III, and IV are evaluated. We found significant differences in mechanical parameters (tissue damping, tissue elasticity, hysteresivity) and increased degrees of non-linear dynamic contributions in the impedance data with increasing degree of obstruction (p < 0.01). The results obtained suggest that the non-linear index correlates better with degrees of heterogeneity linked to COPD GOLD stages, than the currently used hysteresivity index. The protocol and method may prove useful to improve current diagnosis percentages for various COPD phenotypes. [ABSTRACT FROM AUTHOR]

Pulmonary electrical impedance tomography (EIT) is a functional imaging technique that allows real-time monitoring of ventilation distribution. Ventilation heterogeneity (VH) is a characteristic feature of chronic obstructive pulmonary disease (COPD) and has previously been quantified using features derived from tidal variations in the amplitude of the EIT signal. However, VH may be better described by time-based metrics, the measurement of which is made possible by the high temporal resolution of EIT. We aimed 1) to quantify VH using novel time-based EIT metrics and 2) to determine the physiological relevance of these metrics by exploring their relationships with complex lung mechanics measured by the forced oscillation technique (FOT). We performed FOT, spirometry, and tidal-breathing EIT measurements in 11 healthy controls and 9 volunteers with COPD. Through offline signal processing, we derived 3 features from the impedance-time (Z-t) curve for each image pixel: 1) tE, mean expiratory time; 2) PHASE, mean time difference between pixel and global Z-t curves; and 3) AMP, mean amplitude of Z-t curve tidal variation. Distribution was quantified by the coefficient of variation (CV) and the heterogeneity index (HI). Both CV and HI of the tE and PHASE features were significantly increased in COPD compared with controls, and both related to spirometry and FOT resistance and reactance measurements. In contrast, distribution of the AMP feature showed no relationships with lung mechanics. These novel time-based EIT metrics of VH reflect complex lung mechanics in COPD and have the potential to allow real-time visualization of pulmonary physiology in spontaneously breathing subjects. [ABSTRACT FROM AUTHOR]